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Your Environment. Your Health.

Selected Publications

Environmental Genetics Group

Ozone (O3)-induced Pulmonary Injury and Inflammation

  1. Kleeberger SR, Levitt RC, Zhang LY, Longphre M, Harkema J, Jedlicka A, Eleff SM, DiSilvestre D, Holroyd KJ. Linkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice. Nature Genetics 17:475-478, 1997. [Abstract] [ see also, News & Views: The genetics of air pollution, Drazen JM, and Beier DR, Nature Genetics 17:365-366, 1997. [Abstract] ]
  2. Kleeberger SR, Reddy SPM, Zhang LY, Jedlicka AE. Genetic susceptibility to ozone-induced lung hyperpermeability: role of the toll-like receptor 4 (Tlr4). Am J Respir Cell Mol Biol 22:620-627, 2000. [Abstract]
  3. Cho HY, Jedlicka AE, Zhang LY, Kleeberger SR. Ozone-induced lung inflammation and hyperreactivity are mediated via tumor necrosis factor-alpha receptors. Am J Physiol Lung Cell Mol Physiol 280:L537-L546, 2001. [Abstract]
  4. Lay JC, Alexis NE, Kleeberger SR, Roubey RA, Harris BD, Bromberg PA, Hazucha MJ, Devlin RB, Peden DB. Ozone enhances markers of innate immunity and antigen presentation on airway monocytes in healthy individuals. J Allergy Clin Immunol 120(3):719-722, 2007. [Abstract]
  5. Dahl M, Bauer AK, Arredouani M, Soininen R, Trygvasson K, Kleeberger SR, Kobzik L. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II. J Clin Invest 117:757-764, 2007. [Abstract] [see also, Commentary: Scavenger receptors clear the air, EM Postlethwait, J Clin Invest 117:601-604, 2007.] [Abstract]
  6. Cho HY, Morgan DL, Bauer AK, Kleeberger SR. Signal transduction pathways of tumor necrosis factor mediated lung injury induced by ozone in mice. Am J Respir Crit Care Med 175:829-839, 2007. [Abstract]
  7. Yoon HK, Cho HY, Kleeberger SR. Protective role of matrix metalloproteinase-9 in ozone-induced airway inflammation. Environ Health Perspect 115:1557-1563, 2007. [Abstract]
  8. Alexis NE, Zhou H, Lay JC, Harris B, Hernandez ML, Lu T, Bromberg PA, Kleeberger SR, Peden DB. The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in humans. J Allergy Clin Immunol 124:1222-1228, 2009. [Abstract]
  9. Bauer AK, Travis E, Malhotra SS, Rondini EA, Walker C, Cho HY, Trivedi S, Gladwell W, Reddy S, Kleeberger SR. Identification of novel susceptibility genes in ozone-induced inflammation in mice. Eur Respir J 36(2):428-437, 2009. [Abstract]
  10. Bauer AK, Kleeberger SR.  Genetic mechanisms of susceptibility to ozone-induced lung disease. Ann NY Acad Sci 1203:113-119, 2010. [Abstract]
  11. Hernandez, ML, Lay JC, Harris B, Esther CR, Brickey J, Bromberg PA, Diaz-Sanches D, Devlin RB, Kleeberger SR, Alexis NE, Peden DB. Atopic asthmatics but not atopics without asthma have enhanced inflammatory responses to ozone. J Allergy Clin Immunol 126(3):537-544, 2010. [Abstract]
  12. Hernandez ML, B Harris, JC Lay, PA Bromberg, D Diaz-Sanchez, RB Devlin, SR Kleeberger, NE Alexis, and DB Peden.  Comparative airway inflammatory response of normal volunteers to ozone and lipopolysaccharide challenge. Inhal Toxicol 22(8):684-656, 2010. [Abstract]
  13. Backus GS, Howden R, Fostel J, Bauer AK, Cho HY, Marzec J, Peden DB, Kleeberger SR. Protective role of IL-10 in ozone-induced pulmonary inflammation. Environ Health Perspect 118(12):1721-1727, 2010. [Abstract]
  14. Dillon MA, Harris B, Hernandez ML, Zou B, Reed W, Bromberg PA, Devlin RB, Diaz-Sanchez D, Kleeberger SR, Zhou H, Lay JC, Alexis NE, Peden DB. Enhancement of systemic and sputum granulocyte response to inhaled endotoxin in persons with the GSTM1 null genotype. Occupation Environ Med 68(10):783-785, 2011. [Abstract]
  15. Bauer AK, Rondini EA, Hummel K, Degraff LM, Walker C, Jedlicka AE, Kleeberger SR. Identification of candidate genes downstream of TLR4 signaling after ozone exposure in mice: a role for heat-shock protein 70. Environ Health Perspect 119(8):1091-1097, 2011. [Abstract]
  16. Howden R, Kleeberger SR. Genetic and environmental influences on gas exchange. Compr Physiol 2(4):2595-2614, 2012. [Abstract]
  17. Cho HY, Gladwell W, Yamamoto M, Kleeberger SR. Exacerbated airway toxicity of environmental oxidant ozone in mice deficient in Nrf2. Oxid Med Cell Longev 2013:254069, 2013. [Abstract]
  18. Verhein KC, McCaw Z, Gladwell GW, Bushel P, Kleeberger SR. Novel roles for Notch3 and Notch4 receptors in gene expression and susceptibility to ozone-induced lung inflammation in mice. Environ Health Perspect 123:799-805, 2015. [Abstract]

Mechanisms of Susceptibility to Hyperoxia-induced Lung Injury in Adults and Neonates

  1. Cho HY, Jedlicka AE, Reddy SPM, Zhang LY, Kensler TW, Kleeberger SR. Linkage analysis of susceptibility to hyperoxia: Nrf2 is a candidate gene. Am J Respir Cell Mol Biol 26:42-51, 2002. [Abstract]
  2. Cho HY, Jedlicka AE, Reddy SPM, Kensler TW, Yamamoto M, Zhang LY, Kleeberger SR. Role of NRF2 in protection against hyperoxic lung injury in mice. Am J Respir Cell Mol Biol 26:175-182, 2002. [Abstract] [ see also, Perspective: The saga of leucine zippers continues, Otterbein LE, Choi AMK, Am J Respir Cell Mol Biol 26:161-163, 2002. [Abstract] ]
  3. Cho HY, Reddy SPM, Yamamoto M, Kleeberger SR. The transcription factor NRF2 protects against pulmonary fibrosis. FASEB J 18:1258-1260, 2004. [Abstract]
  4. Papaiahgari S, Kleeberger SR, Cho HY, Kalvakolanu DV, Reddy SP. NADPH oxidase and ERK signaling regulate hyperoxia-induced Nrf2-ARE transcriptional response in pulmonary epithelial cells. J Biol Chem 279(40):42302-42312, 2004. [Abstract]
  5. Cho HY, Reddy SPM, DeBiase A, Yamamoto M, Kleeberger SR. Microarray gene expression profiling in oxidative lung injury and NRF2-mediated protection. Free Radical Biology and Medicine 38:325-343, 2005. [Abstract]
  6. Cho H-Y, Reddy SP, Kleeberger SR. NRF2 defends the lung from oxidative stress. Antioxid Redox Signal 8:76-87, 2006. [Abstract]
  7. Marzec J, Christie JD, Reddy SP, Jedlicka AE, Vuong H, Lanken PN, Aplenc R, Yamamoto T, Yamamoto M, Cho HY, Kleeberger SR. Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB J 21:2237-2246, 2007. [Abstract]
  8. Reddy NM, Kleeberger SR, Cho HY, Yamamoto M, Kensler TW, Biswal S, Raddy SP. Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants. Am J Respir Cell Mol Biol 37(1):3-8, 2007. [Abstract]
  9. Wang X, Tomso DJ, Chorley BN, Cho HY, Cheung VG, Kleeberger SR, Bell DA. Identification of polymorphic antioxidant response elements in the human genome. Hum Molec Genet 16:1188-1200, 2007. [Abstract]
  10. Reddy NM, Suryanarayana V, Kalvakolanu DV, Yamamoto M, Kensler TW, Hassoun PM, Kleeberger SR, Reddy SP. Innate immunity against bacterial infection following hyperoxia exposure is impaired in NRF2-deficient mice. J Immunol 183:4601-4608, 2009. [Abstract]
  11. Reddy NM, Suryanaraya V, Yates MS, Kleeberger SR, Hassoun PM, Yamamoto M, Liby KT, Sporn MB, Kensler TW, Reddy SP. The triterpenoid CDDO-imidazolide confers potent protection against hyperoxic acute lung injury in mice. Am J Respir Crit Care Med 180:867-74, 2009. [Abstract]
  12. Reddy AJ, Christie JD, Aplenc R, Fuchs B, Lanken PN, Kleeberger SR. Association of human NAD(P)H:Quinone oxidoreductase 1 polymorphism with development of acute lung injury. J Cell Mol Med 13(8):1784-1791, 2009. [Abstract]
  13. Reddy NM, Kleeberger SR, Kensler, TW, Yamamoto M, Hassoun PM, Reddy SP. Disruption of Nrf2 impairs the resolution of hyperoxia-induced acute lung injury and inflammation in mice. J Immunol 182(11):7264-7271, 2009. [Abstract]
  14. Cho HY, Gladwell W, Wang X, Chorley B, Bell D, Reddy SP, Kleeberger SR. Nrf2-regulated PPAR-γ expression is critical to protection against acute lung injury in mice. Am J Respir Crit Care Med 182(2):170-182, 2010. [Abstract] [ see also accompanying editorial, Reddy RC, Standiford TJ. Nrf2 and PPAR-γ: PPARtnering against oxidant-induced lung injury. Am J Respir Crit Care Med 182(2):134-135. [Abstract] ]
  15. Cho HY, Kleeberger SR. Nrf2 protects against airway disorders. Toxicol Appl Pharmacol 244:43-56, 2010. [Abstract]
  16. Pendyala S, Moitra J, Kalari S, Kleeberger SR, Zhao Y, Reddy SP, Garcia JGN, Natarajan V. NRF2 regulates hyperoxia-induced NOX4 expression in human lung endothelium: identification of functional antioxidant response elements on NOX4 promoter. Free Rad Biol Med 50(12):1749-1759, 2011. [Abstract]
  17. Anwar-Mohamed A, Degenhardt OS, Seubert JM, Kleeberger SR, El-Kadi AO. The effect of Nrf2 knockout on the constitutive expression of drug metabolizing enzymes and transporters in C57Bl/6 mice livers. Toxicol in vitro 25(4):785-795, 2011. [Abstract]
  18. Bauer AK, Cho HY, Miller-DeGraff L, Walker C, Helms K, Fostel J, Yamamoto M, Kleeberger SR. Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice. PLoS One 6(10):e26590, 2011. [Abstract]
  19. Chorley BN, Campbell MR, Wang X, Karaca M, Sambandan D, Bangura F, Xue P, Pi J, Kleeberger SR, Bell DA. Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha. Nucleic Acids Research  40(15):7416-29, 2012. [Abstract]
  20. Howden, R, Cho, HY, Miller-DeGraff, L, Walker, C, Clark, JA, Myers, PH, Rouse, DC, Kleeberger, SR. Cardiac physiologic and genetic predictors of hyperoxia-induced acute lung injury in mice. Am J Respir Cell Mol Biol. 46(4):470-8, 2012. [Abstract]
  21. Cho HY, Van Houten B, Wang X, Miller-DeGraff L, Fostel J, Gladwell W, Perrow L, Panduri V, Kobzik L, Yamamoto M, Bell DA, Kleeberger SR.  Targeted deletion of Nrf2 impairs lung development and oxidant injury in neonatal mice. Antioxid Redox Signal 17(8):1066-82, 2012. [Abstract]
  22. Marczak ED, J Marzec, DC Zeldin, SR Kleeberger, M Pretorius, CR Lee. Functional polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans. Pharmacogenet Genomics 22(8):620-8, 2012. [Abstract]
  23. Howden R, Gougian E, Lawrence M, Cividanes S, Gladwell W, Miller-DeGraff L, Myers PH, Rouse DC, Devlin RB, Cho HY, Kleeberger SR. The influence of Nrf2 on cardiac responses to environmental stressors. Oxid Med Cell Longev 2013:901239, 2013. [Abstract]
  24. Nichols J, Gladwell W, Verhein KC, Cho HY, Wess J, Suzuki O, Wiltshire T, Kleeberger SR. Genome-wide association mapping of acute lung injury in neonatal inbred mice. FASEB J 28(6):2538-2550, 2014. [Abstract]
  25. Cho HY, Kleeberger SR. Perspective: Noblesse oblige: Nrf2 functions in the airways. Am J Respir Cell Mol Biol 50(5):844-847, 2014. [Abstract]
  26. Cho HY, Marzec J, Kleeberger SR. Functional polymorphisms in NRF2: implications for human disease. Free Rad Biol Med, 2015. [Abstract]
  27. Cho HY, Jedlicka AE, Gladwell W, Marzec J, McCaw ZR, Bienstock R, Kleeberger SR. Association of Nrf2 polymorphism haplotypes with acute lung injury phenotypes in mice. Antioxid Redox Signal 22(4):325-338, 2015. [Abstract]
  28. Cho HY, Marzec J, Kleeberger SR. Association of Nrf2 with airway pathogenesis: lessons learned from genetic mouse models. Arch Toxicol, 2015. [Abstract]

Mechanisms of Respiratory Syncytial Virus (RSV) Infection and Disease Severity

  1. Polack FP, Hoffman SJ, Collins PL, Laham FR, Thumar B, Hendry RM, Murphy PM, Randolph V, Karron RA, Kleeberger SR. The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin. Proc Natl Acad Sci USA 125:8996-9001, 2005. [Abstract]
  2. Klein MI, Coviello S, Bauer G, Benitez A, Schiatti MP, Delgado MF, Serra ME, Novalli L, Kleeberger SR, Polack FP. The impact of infection with human metapneumovirus and other viruses in young infants and children at high risk for severe pulmonary disease. J Infect Dis 193:1544-1551, 2006. [Abstract]
  3. Melendi GA, Hoffman SJ, Karron RA, Irusta PM, Laham FR, Humbles A, Schofield B, Pan C, Rabold R, Thumar B, Thumar A, Gerard NP, Mitzner W, Barnum SR, Gerard C, Kleeberger SR, Polack FP. C5 modulates airways hyperreactivity and pulmonary eosinophilia during enhanced respiratory syncytial virus disease by decreasing C3a receptor expression. J Virol 81:991-999, 2007. [Abstract]
  4. Melendi GA, Zavala F, Buchholz UJ, Boivin G, Collins PL, Kleeberger SR, Polack FP. Mapping and characterization of the primary and anamnestic H-2(d)-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus. J Virol 81(20):11461-11467, 2007. [Abstract]
  5. Melendi GA, Laham FR, Monsalvo AC, Casellas JM, Israele V, Polack NR, Kleeberger SR, Polack FP. Cytokine profiles in the respiratory tract during primary infection with human metapneumovirus, respiratory syncytial virus, or influenza in infants. Pediatrics 120:e410-415, 2007. [Abstract]
  6. Klein MI, Bergel E, Coviello S, Bauer G, Benitez A, Serra ME, Delgado MF, Melendi GA, Aspres N, Irusta PM, Rodriguez S, Kleeberger SR, and Polack FP. Differential gender susceptibility to respiratory infections and to the protective effect of breast milk in premature infants. Pediatrics 121:e1510-1516, 2008. [Abstract]
  7. Cho HY, Imani F, Miller-Degraff L, Walters D, Melendi GA, Yamamoto M, Polack FP, Kleeberger SR. Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus (RSV) disease. Am J Respir Crit Care Med 179:138-150, 2009. [Abstract]
  8. Miller EK, Bugna J, Libster R, Shepherd BE, Scalzo PM, Acosta PL, Hijano D, Reynoso N, Batalle JP, Coviello S, Klein MI, Bauer G, Benitez A, Kleeberger SR, Polack FP. Human rhinoviruses in severe respiratory disease in very low birth weight infants. Pediatrics. 129(1):e60-7, 2012. [Abstract]
  9. Ciencewicki J, Wang X, Marzec J, Serra ME, Bell DA, Polack FP, Kleeberger SR. A genetic model of variation and differential susceptibility to human respiratory syncytial virus infection. FASEB J 28(4):1947-1956, 2014. [Abstract]
  10. Caballero MT, Serra ME, Acosta PL, Marzec J, Gibbons L, Salim M, Rodriques A, Reynaldi A, Garcia A, Bado D, Buchholz UJ, Hijano DR, Coviello S, Newcomb D, Bellabarba M, Ferolla FM, Libster R, Berenstein A, Siniawaski S, Blumetti V, Echavarria M, Pinto L, Lawrence A, Ossorio MF, Grosman A, Mateu CG, Bayle C, Dericco A, Pellegrini M, Igarza I, Reppeto HA, Grimaldi LA, Gudapati P, Polack NR, Althabe F, Shi M, Ferrero F, Bergel E, Stein RS, Peebles RS, Boothby M, Kleeberger SR, Polack FP. TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization. J Clin Invest 125(2):571-582, 2015. [Abstract]

Mechanisms of Susceptibility to Lung Tumorigenesis

  1. Bauer A, Malkinson A, Kleeberger SR. Susceptibility to neoplastic and non-neoplastic pulmonary diseases in mice: genetic similarities. Am J Physiol Lung Cell Mol Physiol 287:L685-L703, 2004. [Abstract]
  2. Bauer AK, Fostel J, Degraff LM, EA Rondini, C Walker, S Grissom, J Foley, Kleeberger SR. Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis. J Natl Cancer Inst (JNCI) 97:1778-1781, 2005. [Abstract]
  3. Bauer AK, Fostel J, DeGraff LM, Rondini EA, Walker C, Grissom SF, Foley J, Kleeberger SR. Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis. Mol Cancer 19;8:107, 2009. [Abstract]
  4. Wang X, Chorley BN, Pittman GS, Kleeberger SR, Brothers 2nd J, Liu G, Spira A, Bell DA.  Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer. PLoS One 5(8):e11934, 2010. [Abstract]
  5. Sissung TM, Gardner ER, Piekarz RL, Howden R, Chen X, Woo S, Franke RM, Clark JA, Miller-Degraff L, Steinberg SM, Venzon D, Liewehr DJ, Kleeberger SR, Bates SE, Price DK, Rosing DR, Cabell C, Sparreboom A, Figg WD. Impact of ABCB1 allelic variants on QTc interval prolongation. Clin Cancer Res 17(4):937-946, 2011. [Abstract]
  6. Bauer AK, Cho HY, Miller-DeGraff L, Walker C, Helms K, Fostel J, Yamamoto M, Kleeberger SR. Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice. PLoS One 6(10):e26590, 2011. [Abstract]